A-834,735 Explained

A-834,735 is a drug developed by Abbott Laboratories that acts as a potent cannabinoid receptor full agonist at both the CB₁ and CB₂ receptors, with a K_i of 12 nM at CB₁ and 0.21 nM at CB₂. Replacing the aromatic 3-benzoyl or 3-naphthoyl group found in most indole derived cannabinoids with the 3-tetramethylcyclopropylmethanone group of A-834,735 and related compounds imparts significant selectivity for CB₂, with most compounds from this group found to be highly selective CB₂ agonists with little affinity for CB₁. However, low nanomolar CB₁ binding affinity is retained with certain heterocyclic 1-position substituents such as (N-methylpiperidin-2-yl)methyl (cf. AM-1220, AM-1248), or the (tetrahydropyran-4-yl)methyl substituent of A-834,735, resulting in compounds that still show significant affinity and efficacy at both receptors despite being CB₂ selective overall.^{[1] [2] [3] [4] [5]}

Legal status

As of October 2015 A-834,735 is a controlled substance in China.^[6]

See also

• A-796,260
• AB-001
• AB-005
• FUB-144
• JTE 7-31
• UR-144
• XLR-11

Notes and References

1. Dart M, Frost J, Tietje K, Daza A, Grayson G, Fan Y, Mukherjee S, Garrison TR, Yao B, Meyer M . 6 . 2006 . 1-Alkyl-3-keto-indoles: identification and in vitro characterization of a series of potent cannabinoid ligands. . 2006 Symposium on the Cannabinoids . International Cannabinoid Research Society . Burlington, VT .
2. Poso A, Huffman JW . Targeting the cannabinoid CB2 receptor: modelling and structural determinants of CB2 selective ligands . British Journal of Pharmacology . 153 . 2 . 335–46 . January 2008 . 17982473 . 2219524 . 10.1038/sj.bjp.0707567 .
3. Chin CL, Tovcimak AE, Hradil VP, Seifert TR, Hollingsworth PR, Chandran P, Zhu CZ, Gauvin D, Pai M, Wetter J, Hsieh GC, Honore P, Frost JM, Dart MJ, Meyer MD, Yao BB, Cox BF, Fox GB . 6 . Differential effects of cannabinoid receptor agonists on regional brain activity using pharmacological MRI . British Journal of Pharmacology . 153 . 2 . 367–79 . January 2008 . 17965748 . 2219521 . 10.1038/sj.bjp.0707506 .
4. Frost JM, Dart MJ, Tietje KR, Garrison TR, Grayson GK, Daza AV, El-Kouhen OF, Miller LN, Li L, Yao BB, Hsieh GC, Pai M, Zhu CZ, Chandran P, Meyer MD . 6 . Indol-3-yl-tetramethylcyclopropyl ketones: effects of indole ring substitution on CB2 cannabinoid receptor activity . Journal of Medicinal Chemistry . 51 . 6 . 1904–12 . March 2008 . 18311894 . 10.1021/jm7011613 .
5. Frost JM, Dart MJ, Tietje KR, Garrison TR, Grayson GK, Daza AV, El-Kouhen OF, Yao BB, Hsieh GC, Pai M, Zhu CZ, Chandran P, Meyer MD . 6 . Indol-3-ylcycloalkyl ketones: effects of N1 substituted indole side chain variations on CB(2) cannabinoid receptor activity . Journal of Medicinal Chemistry . 53 . 1 . 295–315 . January 2010 . 19921781 . 10.1021/jm901214q .
6. Web site: 关于印发《非药用类麻醉药品和精神药品列管办法》的通知 . China Food and Drug Administration . 27 September 2015 . Chinese . 1 October 2015 . https://web.archive.org/web/20151001222554/http://www.sfda.gov.cn/WS01/CL0056/130753.html . 1 October 2015 . dead .